We found that Muse Mammary Tumor Virus, a betaretrovirus spread through the milk, requires commensal microbiota for successful transmission. The virus exploits bacterially-produced lipopolysaccharide to elicit immunosuppressive cytokines and thus, counteract anti-virus immune response. Our studies will uncover the rules of retrovirus-microbiota-host interaction by using genetically defined and germ-free mice.